C7 substituted oxysterols and methods of use thereof

Abstract

Compounds are provided according to Formula (A): and pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof; wherein R 1A , R 1B , n, R 2A , R 2B , R 3 , and R 4 are as defined herein. Compounds of the present invention are contemplated useful for the prevention and treatment of a variety of conditions.

What is claimed is: 
     
       1. A method of treating a CNS-related condition, wherein the CNS-related condition is related to NMDA-modulation and is selected from the group consisting of an adjustment disorder, anxiety disorder, cognitive disorder, dissociative disorder, eating disorder, mood disorder, schizophrenia or other psychotic disorder, sleep disorder, substance-related disorder, personality disorder, autism spectrum disorders, neurodevelopmental disorder, multiple sclerosis, sterol synthesis disorders, pain, encephalopathy secondary to a medical condition, seizure disorder, stroke, traumatic brain injury, movement disorder, vision impairment, hearing loss, or tinnitus, comprising administering to a subject in need thereof an effective amount of a compound of Formula (B): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein:
 each of R 1a  and R 1B  is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted carbocyclyl, wherein the carbocyclyl may be saturated or partially saturated, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, or R 1A  and R 1B , together with the carbon atom to which they are attached form a 3-8 membered ring; 
 n is 1 or 2; 
 each of R 2A  and R 2B  is independently hydrogen, halo, —OR C , substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl, wherein R C  is hydrogen or substituted or unsubstituted alkyl, or R 2A  and R 2B , together with the carbon atom to which they are attached form an oxo group, wherein R 2A  and R 2B  are not both simultaneously hydrogen; 
 R 3  is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, or —OR A , wherein R A  is substituted or unsubstituted alkyl; 
 R 4  is absent or hydrogen; and 
    represents a single or double bond, wherein when one of   is a double bond, the other   is a single bond; when both of   are single bonds, then R 4  is hydrogen; and when one of the   is a double bond, R 4  is absent, or 
 a pharmaceutical composition comprising said compound of Formula (B) or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier. 
 
       
     
     
       2. The method according to  claim 1 , wherein n is 1. 
     
     
       3. The method according to  claim 1 , where n is 2. 
     
     
       4. The method according to  claim 1 , wherein each of R 1A  and R 1B  is independently unsubstituted or substituted alkyl. 
     
     
       5. The method according to  claim 1 , wherein each of R 1A  and R 1B  is independently selected from the group consisting of haloalkyl, alkoxyalkyl, —CH 3 , —CH 2 CH 3 , —CH(CH 3 ) 2 , —CF 3  and —CH 2 OCH 3 . 
     
     
       6. The method according to  claim 1 , wherein R 1A  and R 1B , together with the carbon atom to which they are attached form a 3-8 membered ring. 
     
     
       7. The method according to  claim 1 , wherein R 1A  is hydrogen and R 1B  is alkyl, carbocyclyl, heterocyclyl, aryl, or heteroaryl. 
     
     
       8. The method according to  claim 1 , wherein each of R 2A  and R 2B  is independently substituted or unsubstituted alkyl. 
     
     
       9. The method according to  claim 1 , wherein R 3  is substituted or unsubstituted alkyl. 
     
     
       10. The method according to  claim 1 , wherein the compound is selected from the group consisting of 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
       11. The method according to  claim 1 , wherein the compound is a pharmaceutically acceptable salt of a compound selected from the group consisting of: